After attending Sciences Po Aix and ENA, France's elite graduate school of public affairs, she worked in Jacques Delors' staff in 1982 before being hired by Hubert Védrine in François Mitterrand's government.

She co-sponsored a 1998 law which abrogated the requirement of "manifestation of will" for children born in France of foreign parents to gain citizenship.

[2] Also in the late 1990s, she took action to grant investigating magistrates more independence; at the same time, she gave the Justice Ministry the ability to intervene.

[3] Guigou also co-sponsored a 2000 law which articulated the French policy on presumption of innocence in media by prohibiting magazines and newspapers from publishing photographs of accused individuals wearing handcuffs or other scenes which may "jeopardise a victim's dignity".

[7] Guigou failed to be elected Mayor of Avignon and, facing possible defeat against Marie-Josée Roig in her district, was nominated as a candidate for the National Assembly in 2002 in the heavily left-wing département of Seine-Saint-Denis.

[13] From 2015, Guigou served as a member of the European Commission's High-level Group of Personalities on Defence Research chaired by Elżbieta Bieńkowska.

[14] In December 2020, Guigou was named by Secretary of State for Child protection Adrien Taquet to lead a government-mandated committee on sexual violence against children.

[15][16] Amid revelations about sexual assault involving her friend Olivier Duhamel, Guigou resigned from that role in January 2021.

In December 2014, Guigou raised international media attention by sponsoring a resolution to ask the French government to recognise Palestine.